Title:Preclinical Pharmacokinetics and Pharmacology Study of RC98: A
Programmed Cell Death Ligand 1 Monoclonal Antibody in Cynomolgus
Monkeys
Volume: 30
Issue: 16
Author(s): Ling Wang, Qiaoning Li, Chenglian Deng, Zhihao Liu, Fang Wang, Shenjun Li, Lihou Dong and Jing Jiang*
Affiliation:
- Rongchang Industry College, Yantai
264003, Shandong, China
- Department
of Pharmacology, Binzhou Medical University, Yantai 264003, Shandong, China
Keywords:
RC98, pharmacokinetic, receptor occupancy, T cell-dependent antibody response, soluble PD-L1, cynomolgus monkeys.
Abstract:
Introduction: RC98 is the monoclonal antibody against Programmed Cell Death Ligand 1 (PD-L1).
Relevant reports have confirmed that the influence of PD-L1 expressed by tumor cells on antitumor CD8+ T
cell responses is well characterized, but the impact of PD-L1 expressed by immune cells has not been well
defined.
Objective: This study aimed to design a Pharmacokinetics/Pharmacology (PK/PD) study of RC98 in normal
cynomolgus monkeys to research the effect on the immune system.
Methods: RC98 and vehicle were administered to cynomolgus monkeys at 15 mg/kg via intravenous infusion
once a week for 4 weeks to evaluate the relationship between PK and PD. The pharmacodynamic activity was
measured by the PD-L1 receptor occupancy (RO) in CD3+ T cells, A T-cell-dependent antibody response (TDAR),
and the concentration of soluble PD-L1.
Results: The pharmacokinetic result showed that the exposure from the last administration was lower than that
of the first administration, probably due to immunogenicity production. There was a strong correlation between
systemic exposure and RO in CD3+ T cells but decreased RO levels after the last dose, which indirectly
reflected the activation of T cells. The keyhole limpet hemocyanin (KLH)-induced TDAR in the RC98 group
was higher than in the vehicle group. The concentration of soluble PD-L1 had increased feedback with RC98,
and the concentration of soluble PD-L1 was maintained at a higher level after multiple doses than before dosing.
Conclusion: These data indicate that the immune system was clearly activated. In addition, the non-clinical data
could provide a basis for its efficacy evaluation in clinical trials.
